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Fung2005_Metabolic_Oscillator

ABSTRACT: A Synthetic Gene-Metabolic Oscillator Reference: Fung et al; Nature (2005) 435:118-122 Name of kinetic law Reaction Glycolytic flux, V_gly: nil -> AcCoA; Flux to TCA cycle/ETOH, V_TCA: AcCoA -> TCA/EtOH; HOAc ex/import,reversible, V_out: HOAc -> HOAc_E V_Pta: AcCoA + Pi -> AcP + CoA reversible, V_Ack: AcP + ADP -> OAc + ATP V_Acs: OAC + ATP -> AcCoA +PPi Acetic acid-base equillibrium, reversible, V_Ace: OAC + H -> HOAc Expression of LacI, R_LacI: nil -> LacI Expression of Acs, R_Acs: nil -> Acs Expression of Pta, R_Pta: nil -> Pta LacI degradation, R_dLacI: LacI -> nil Acs degradation, R_dAcs: Acs -> nil Pta degradation, R_dPta: Pta -> nil For this model the differential equation for V_Ace was changed from: C*(AcP*H-K_eq*OAC) with C = 100 in the supplemental material to C*(OAc*H-K_eq*HOAc) with C = 100, as in Bulter et. al; PNAS(2004),101,2299-2304 , and a value for K_eq of 5*10^-4 after communication with the authors. translated to SBML by: Lukas Endler(luen at tbi.univie.ac.at), Christoph Flamm (xtof at tbi.univie.ac.at) Biomodels Curation The model reproduces 3a of the paper for glycolytic flux Vgly = 0.5. The authors have agreed that the values on Y-axis are marked wrong and hence there is a discrepancy between model simulation results and the figure. Also, note that the values of concentration and time are in dimensionless units. The model was successfully tested on MathSBML and Jarnac.

SUBMITTER: Harish Dharuri

PROVIDER: BIOMD0000000067 | BioModels | 2006-08-28

REPOSITORIES: BioModels

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Publications

A synthetic gene-metabolic oscillator.

Fung Eileen E Wong Wilson W WW Suen Jason K JK Bulter Thomas T Lee Sun-gu SG Liao James C JC

Nature 20050501 7038

Autonomous oscillations found in gene expression and metabolic, cardiac and neuronal systems have attracted significant attention both because of their obvious biological roles and their intriguing dynamics. In addition, de novo designed oscillators have been demonstrated, using components that are not part of the natural oscillators. Such oscillators are useful in testing the design principles and in exploring potential applications not limited by natural cellular behaviour. To achieve transcri ...[more]

PMID: 15875027

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Project description:Malic enzymes decarboxylate the tricarboxylic acid (TCA) cycle intermediate malate to the glycolytic end-product pyruvate and are well positioned to regulate metabolic flux in central carbon metabolism. The bacterium Sinorhizobium meliloti has a NAD(P)-malic enzyme (DME) and a NADP-malic enzyme (TME) and DME is required for symbiotic N2-fixation. To help understand the role of these enzymes, we examined growth, metabolic and transcriptional consequences resulting from the deletion of these enzymes. Few effects were observed upon growth with glucose, whereas growth with the gluconeogenic substrate, succinate, resulted in transcriptional and metabolic effects particularly in the dme mutant strains. When grown with succinate, DME mutant cells accumulated hexose sugar phosphates and trehalose, while TME mutants accumulated putrescine. Succinate-grown DME mutant cells also showed increased transcription of genes for gluconeogenesis and for pathways such as amino acid and fatty acid synthesis that divert metabolites away from the TCA cycle. These data suggested that, DME is required to regulate the levels of TCA cycle intermediates and that the activity of TME is insufficient to prevent the accumulation of TCA cycle intermediates in cells utilizing succinate as carbon source. Consistent with this, in short-1-3 hour incubations with succinate, dme mutant cells excreted large amounts of malate whereas little malate was excreted from tme or wild-type cells. These results support the suggestion that DME is required for N2-fixation in alfalfa because it is required for synthesis of pyruvate and acetyl-CoA and the rapid metabolism of C4-dicarboxylates supplied by the plant. RNA expression was measured for S. meliloti in exponential phase grown in MOPS (morpholinpropanesulfonic acid) buffered minimal media under 2 growth conditions: 1) 15 mM succinate, 2) 15 mM glucose; using wild type cells as well as dme and tme mutant strains (6 experiments, 2 replicates: total 12 samples)

Dataset Information

Fung2005_Metabolic_Oscillator

Publications

A synthetic gene-metabolic oscillator.

Similar Datasets

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